Alcoholic liver and pancreatic diseases (ALPD) and cirrhosis constitute leading life-style diseases around the globe. The Southern California Research Center for ALPD and Cirrhosis unifies 57 investigators from major academic institutions in Southern California to pursue a common mission of being a leader in research, training, and outreach for the diseases. The center, since its inception in 1999, has devoted its efforts for development and use of clinically relevant animal models to gain novel insights into the molecular mechanisms underlying the predisposition to advanced ALPD. These efforts culminated to recent groundbreaking discoveries which have significantly advanced our understanding of synergistic ALPD caused by alcohol and a second hit. The center's interactive environment and infrastructure have facilitated in the past 5 years, a 152% increase in research base to $8.5M/year; 4 new U01/P01 programs; 198 publications; generation of 14 NIH-funded early-stage investigators; transition of 8 postdocs to faculty positions; training 166 graduate and 20 undergraduate students; and organizing 3 community seminars and 4 international symposia. As a unique national resource, the center has provided to scientific communities across the nation: 229 rodents as ALPD models and 241 model samples for 17 outside investigators; 329 liver cell isolation preparations for 14 investigators; and support for grant acquisition and application by 12 outside investigators since the last renewal. The center will continue to strive as a unique scientific center of excellence in ALPD and cirrhosis by promoting: 1) environment conducive for leading-edge research on the center's theme: elucidation of the priming and sensitizing mechanisms for ALPD; 2) provision of unique models, innovative genetic approaches and expertise to outside investigators including those at other NIAAA Alcohol Research Centers; 3) comprehensive education and training to foster future generations of scientists in ALPD and cirrhosis; and 4) outreach efforts to disseminate the center's new findings to lay public, health care workers and scientists in our home and global communities.